The Presence of Peripheral Inflammatory Markers in Patients with Major Depressive Disorder, the Associated Symptoms Profiles and the Antidepressant Efficacy of Celecoxib (original) (raw)
Related papers
No increase in inflammation in late-life major depression screened to exclude physical illness
Translational Psychiatry, 2022
Depression is a common and debilitating disorder in the elderly. Late-life depression (LLD) has been associated with inflammation and elevated levels of proinflammatory cytokines including interleukin (IL)-1β, tumor necrosis factor-alpha, and IL-6, but often depressed individuals have comorbid medical conditions that are associated with immune dysregulation. To determine whether depression has an association with inflammation independent of medical illness, 1120 adults were screened to identify individuals who had clinically significant depression but not medical conditions associated with systemic inflammation. In total, 66 patients with LLD screened to exclude medical conditions associated with inflammation were studied in detail along with 26 age-matched controls (HC). At baseline, circulating cytokines were low and similar in LLD and HC individuals. Furthermore, cytokines did not change significantly after treatment with either an antidepressant (escitalopram 20 mg/day) or an antidepressant plus a COX-2 inhibitor or placebo, even though depression scores improved in the non-placebo treatment arms. An analysis of cerebrospinal fluid in a subset of individuals for IL-1β using an ultrasensitive digital enzyme-linked immunosorbent assay revealed low levels in both LLD and HC at baseline. Our results indicate that depression by itself does not result in systemic or intrathecal elevations in cytokines and that celecoxib does not appear to have an adjunctive antidepressant role in older patients who do not have medical reasons for having inflammation. The negative finding for increased inflammation and the lack of a treatment effect for celecoxib in this carefully screened depressed population taken together with multiple positive results for inflammation in previous studies that did not screen out physical illness support a precision medicine approach to the treatment of depression that takes the medical causes for inflammation into account.
Connection between inflammatory markers, antidepressants and depression
Acta clinica Croatica
The aim of this study was to explore the role of inflammatory markers in the occurrence of depression. The concentrations of inflammatory markers were analyzed in the groups of healthy subjects and subjects with major depressive disorder (MDD) initially and after one-month antidepressant therapy in the latter. The intention was to demonstrate the role of inflammatory markers in the development of MDD by differences in their concentrations and to explain the mechanism of depression development. This would help us expand our understanding of the occurrence of depression and enable introduction of some new methods in the treatment and diagnosis of depression. Study results showed a statistically significant difference in the concentrations of inflammatory markers (C-reactive protein (CRP), interleukin-6 and tumor necrosis factor alpha) between the group of MDD subjects and control group of healthy subjects. These concentrations were higher in MDD subjects. A statistically significant d...
2019
Background: Major depressive disorder (MDD) is a disabling health problem with a very high global prevalence and burden. Alteration of inflammatory markers in depression is of growing interest to many psychiatry researchers. This study aimed to examine the serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in MDD patients to find out their association with depression. Materials and methods: The present study recruited 88 MDD patients and 86 control subjects matched by age, gender, and body mass index (BMI). The Hamilton depression rating scale (Ham-D) was used on all patients to measure their severity of depression. Serum levels of IL-6 and CRP were analyzed by commercially available enzyme-linked immunosorbent assay (ELISA) kits (Abcam, Cambridge, MA, USA). Results: The mean values of serum levels of IL-6 and CRP were 2.94 ± 0.12 pg/mL and 0.99 ± 0.02 mg/L for the patient group and 2.42 ± 0.21 pg/mL and 1.09 ± 0.06 mg/L for the control group, respectively. We found significantly elevated concentrations of serum IL-6 in MDD patients compared with control subjects (p < 0.001). However, the alteration of serum CRP levels was not significant between the groups (p = 0.126). Ham-D scores of patients were positively correlated with serum IL-6 (r = 0.552; p = 0.004) and CRP (r = 0.621; p < 0.001) levels. Moreover, serum IL6 and CRP levels were observed to be positively correlated (r = 0.452; p = 0.043) with each other in depression. Conclusions: The present study suggests that increased serum IL-6 level might be a contributing factor to the pathogenesis of depression.
Journal of Evolution of Medical and Dental Sciences, 2016
BACKGROUND Studies indicate that along with many other factors, low grade inflammation may play an important contributory role in the development of major depressive psychosis. This may add up as a confounding factor for different complications related to this major psychological disorder. The role of hsCRP as a marker of low grade inflammation has been explored and analysed in the present study. METHODS HsCRP, Total Cholesterol (TC), Triglyceride (TG) and Fasting Blood Glucose (FBG) were measured in 49 cases of major depression against 40 age and body weight (BMI) matched control subjects. The degree of depression in the case group was assessed by the HAM-D score. Data were analysed for any differences in these parameters between the case and control groups followed by correlation and regression analysis to assess the strength of association between the study parameters and the predictive values of serum cholesterol, triglyceride, FBG and HAM-D score on hsCRP. RESULTS HsCRP, TC and TG were significantly higher in the case group. The correlation and regression analyses revealed that hsCRP was strongly associated (r=0.559, P <0.001) and dependent (beta=0.579, P <0.001) on the HAM-D score only. CONCLUSION These results not only indicate a definite association of low grade inflammation with major depressive psychosis, but also suggest a close linear relationship between this low grade inflammation and the degree of depression. The researchers propose that hsCRP is a good indicator for monitoring the pro-inflammatory status and the degree of severity of the disease process in major depressive psychosis.
Journal of Contemporary Medical Education, 2015
Major depressive disorder (MDD) is an important cause of disability and only about 50% of patients achieve remission with standard antidepressant treatment. There is evidence that inflammatory mechanisms mediate the development and progression of this disease. However, controversy remains about the use of anti-inflammatory drugs as a therapeutic option for MDD. Research Hypothesis: Patients with MDD who receive celecoxib plus standard therapy achieve a lower score in the Hamilton rating scale for depression (HRSD) when compared to placebo plus standard therapy. Methods: A total of 80 out-patients from the Mental Health Service of the Fundacion Santa Fe de Bogotá, aged 20-40 years old, with a diagnosis of moderate or severe MDD without previous treatment in the last 6 months will be included. Patients will be randomized to Celecoxib or placebo with an allocation ratio of 1:1 using a web-based random number generator. The primary endpoint will be the difference between the pretest and posttest score of the HRSD, after 6 months of treatment. Feasibility: This trial is feasible and relevant to the theme, in spite of the difficulty to maintain adherence in a study with MDD. Anticipated Results: Decrease in HRSD is expected in both groups during follow-up, but it is expected to be larger in the celecoxib group. A more rapid decrease of HRSD scores is expected in the 1 st weeks.
CNS spectrums, 2023
Objective. There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). Methods. In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20 mg daily for 8 weeks. Responders continued escitalopram while nonresponders received adjunctive aripiprazole 2-10 mg daily for 8 weeks. Plasma levels of proinflammatory markers-C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. Results. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. Conclusion. Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with nonresponse to adjunctive aripiprazole. These findings require validation in independent clinical populations.
Neuropsychopharmacology, 2014
Although anxiety disorders, like depression, are increasingly being associated with metabolic and cardiovascular burden, in contrast with depression, the role of inflammation in anxiety has sparsely been examined. This large cohort study examines the association between anxiety disorders and anxiety characteristics with several inflammatory markers. For this purpose, persons (18-65 years) with a current (N ¼ 1273) or remitted (N ¼ 459) anxiety disorder (generalized anxiety disorder, social phobia, panic disorder, agoraphobia) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and healthy controls (N ¼ 556) were selected from the Netherlands Study of Depression and Anxiety. In addition, severity, duration, age of onset, anxiety subtype and co-morbid depression were assessed. Inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6 and tumor-necrosis factor (TNF)-a. Results show that after adjustment for sociodemographics, lifestyle and disease, elevated levels of CRP were found in men, but not in women, with a current anxiety disorder compared with controls (1.18 (s.e. ¼ 1.05) versus 0.98 (s.e. ¼ 1.07) mg l À 1 , P ¼ 0.04, Cohen's d ¼ 0.18). No associations were found with IL-6 or TNF-a. Among persons with a current anxiety disorder, those with social phobia, in particular women, had lower levels of CRP and IL-6, whereas highest CRP levels were found in those with an older age of anxiety disorder onset. Especially in persons with an age of onset after 50 years, CRP levels were increased compared with controls (1.95 (s.e. ¼ 1.18) versus 1.27 (s.e. ¼ 1.05) mg l À 1 , P ¼ 0.01, Cohen's d ¼ 0.37). In conclusion, elevated inflammation is present in men with current anxiety disorders. Immune dysregulation is especially found in persons with a late-onset anxiety disorder, suggesting the existence of a specific late-onset anxiety subtype with a distinct etiology, which could possibly benefit from alternative treatments.
Depression and Anxiety, 2009
Background: The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses. Cyclooxygenase-2 inhibitors such as celecoxib reduce the production of pro-inflammatory cytokines. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six-week double blind and placebo controlled trial. Methods: Forty adult outpatients who met the DSM-IV-TR criteria for major depression participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. Patients were allocated in a random fashion: 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 20 to fluoxetine 40 mg/day plus placebo. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4, and 6 weeks after the medication started. Results: Although both protocols significantly decreased the score of Hamilton Rating Scale for Depression over the trial period, the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression. There were no significant differences in the two groups in terms of observed side effects. Conclusion: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti-inflammatory therapies should be further investigated. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc.
BMJ open, 2018
Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sen...